| IED ID | IndEnz0005000004 |
| Enzyme Type ID | lipase000004 |
| Protein Name |
Pancreatic lipase-related protein 2 PL-RP2 Cytotoxic T lymphocyte lipase Galactolipase EC 3.1.1.26 Triacylglycerol lipase EC 3.1.1.3 |
| Gene Name | PNLIPRP2 PLRP2 |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MLPPWTLGLLLLATVRGKEVCYGQLGCFSDEKPWAGTLQRPVKLLPWSPEDIDTRFLLYTNENPNNFQLITGTEPDTIEASNFQLDRKTRFIIHGFLDKAEDSWPSDMCKKMFEVEKVNCICVDWRHGSRAMYTQAVQNIRVVGAETAFLIQALSTQLGYSLEDVHVIGHSLGAHTAAEAGRRLGGRVGRITGLDPAGPCFQDEPEEVRLDPSDAVFVDVIHTDSSPIVPSLGFGMSQKVGHLDFFPNGGKEMPGCKKNVLSTITDIDGIWEGIGGFVSCNHLRSFEYYSSSVLNPDGFLGYPCASYDEFQESKCFPCPAEGCPKMGHYADQFKGKTSAVEQTFFLNTGESGNFTSWRYKISVTLSGKEKVNGYIRIALYGSNENSKQYEIFKGSLKPDASHTCAIDVDFNVGKIQKVKFLWNKRGINLSEPKLGASQITVQSGEDGTEYNFCSSDTVEENVLQSLYPC |
| Enzyme Length | 469 |
| Uniprot Accession Number | P54317 |
| Absorption | |
| Active Site | ACT_SITE 171; /note="Nucleophile"; /evidence="ECO:0000269|PubMed:18702514"; ACT_SITE 195; /note="Charge relay system"; /evidence="ECO:0000255|PROSITE-ProRule:PRU10037, ECO:0000269|PubMed:18702514"; ACT_SITE 282; /note="Charge relay system"; /evidence="ECO:0000255|PROSITE-ProRule:PRU10037, ECO:0000269|PubMed:18702514" |
| Activity Regulation | ACTIVITY REGULATION: Regulated by CLPS and bile salts levels ranging 1-5 mM in neonates and 2-30 mM in healthy adults. CLPS stimulates milk fat digestion in the presence of 4 mM bile salts (PubMed:23732775). Triacylglycerol lipase activity toward short- and medium-chain triglycerides is inhibited by increasing concentrations of bile salts and weakly reactivated by CLPS (PubMed:15287741, PubMed:17401110, PubMed:21652702, PubMed:26494624). Optimal triacylglycerol lipase activity is reached at bile salts concentrations ranging from 0.1 to 0.5 mM and then decreases at concentrations higher than 1 mM (PubMed:21652702, PubMed:15287741, PubMed:17401110). Lipase activity toward long-chain glycerolipids is stimulated by CLPS in the presence of 4 mM bile salts (PubMed:21652702). Galactolipase activity is inhibited at high concentrations of bile salts (PubMed:20083229). Triacylglycerol lipase activity is inhibited by anti-obesity drug tetrahydrolipstatin (PubMed:17401110). {ECO:0000269|PubMed:15287741, ECO:0000269|PubMed:17401110, ECO:0000269|PubMed:20083229, ECO:0000269|PubMed:21652702, ECO:0000269|PubMed:23732775, ECO:0000269|PubMed:26494624}. |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=a triacylglycerol + H2O = a diacylglycerol + a fatty acid + H(+); Xref=Rhea:RHEA:12044, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17855, ChEBI:CHEBI:18035, ChEBI:CHEBI:28868; EC=3.1.1.3; Evidence={ECO:0000269|PubMed:15287741, ECO:0000269|PubMed:17401110, ECO:0000269|PubMed:18702514, ECO:0000269|PubMed:19451396, ECO:0000269|PubMed:21652702, ECO:0000269|PubMed:21865348, ECO:0000269|PubMed:26494624};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12045; Evidence={ECO:0000305|PubMed:15287741, ECO:0000305|PubMed:17401110, ECO:0000305|PubMed:18702514, ECO:0000305|PubMed:19451396, ECO:0000305|PubMed:21652702, ECO:0000305|PubMed:21865348, ECO:0000305|PubMed:26494624}; CATALYTIC ACTIVITY: Reaction=a 1,2-diacyl-3-O-(beta-D-galactosyl)-sn-glycerol + 2 H2O = 3-beta-D-galactosyl-sn-glycerol + 2 a fatty acid + 2 H(+); Xref=Rhea:RHEA:13189, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15754, ChEBI:CHEBI:17615, ChEBI:CHEBI:28868; EC=3.1.1.26; Evidence={ECO:0000269|PubMed:15287741, ECO:0000269|PubMed:17401110, ECO:0000269|PubMed:18702514, ECO:0000269|PubMed:20083229};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13190; Evidence={ECO:0000305|PubMed:15287741, ECO:0000305|PubMed:17401110, ECO:0000305|PubMed:18702514, ECO:0000305|PubMed:20083229}; CATALYTIC ACTIVITY: Reaction=1,2,3-tri-(9Z-octadecenoyl)-glycerol + H2O = (9Z)-octadecenoate + di-(9Z)-octadecenoylglycerol + H(+); Xref=Rhea:RHEA:38575, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30823, ChEBI:CHEBI:53753, ChEBI:CHEBI:75945; Evidence={ECO:0000269|PubMed:18702514, ECO:0000269|PubMed:19451396, ECO:0000269|PubMed:21652702, ECO:0000269|PubMed:21865348, ECO:0000269|PubMed:26494624};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38576; Evidence={ECO:0000305|PubMed:18702514, ECO:0000305|PubMed:19451396, ECO:0000305|PubMed:21652702, ECO:0000305|PubMed:21865348, ECO:0000305|PubMed:26494624}; CATALYTIC ACTIVITY: Reaction=di-(9Z)-octadecenoylglycerol + H2O = (9Z)-octadecenoate + (9Z-octadecenoyl)-glycerol + H(+); Xref=Rhea:RHEA:47868, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30823, ChEBI:CHEBI:75937, ChEBI:CHEBI:75945; Evidence={ECO:0000269|PubMed:21865348};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47869; Evidence={ECO:0000305|PubMed:21865348}; CATALYTIC ACTIVITY: Reaction=(9Z-octadecenoyl)-glycerol + H2O = (9Z)-octadecenoate + glycerol + H(+); Xref=Rhea:RHEA:39955, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:30823, ChEBI:CHEBI:75937; Evidence={ECO:0000269|PubMed:18702514, ECO:0000269|PubMed:21865348};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39956; Evidence={ECO:0000305|PubMed:18702514, ECO:0000305|PubMed:21865348}; CATALYTIC ACTIVITY: Reaction=1-(9Z-octadecenoyl)-glycerol + H2O = (9Z)-octadecenoate + glycerol + H(+); Xref=Rhea:RHEA:38487, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:30823, ChEBI:CHEBI:75342; Evidence={ECO:0000269|PubMed:17401110, ECO:0000269|PubMed:18702514};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38488; Evidence={ECO:0000305|PubMed:17401110, ECO:0000305|PubMed:18702514}; CATALYTIC ACTIVITY: Reaction=1,2,3-tripropanoylglycerol + H2O = dipropanoylglycerol + H(+) + propanoate; Xref=Rhea:RHEA:48024, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17272, ChEBI:CHEBI:88153, ChEBI:CHEBI:88155; Evidence={ECO:0000269|PubMed:18702514};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48025; Evidence={ECO:0000305|PubMed:18702514}; CATALYTIC ACTIVITY: Reaction=1,2,3-tributanoylglycerol + H2O = butanoate + dibutanoylglycerol + H(+); Xref=Rhea:RHEA:40475, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17968, ChEBI:CHEBI:35020, ChEBI:CHEBI:76478; Evidence={ECO:0000269|PubMed:15287741, ECO:0000269|PubMed:17401110, ECO:0000269|PubMed:18702514, ECO:0000269|PubMed:21652702, ECO:0000269|PubMed:26494624};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40476; Evidence={ECO:0000305|PubMed:15287741, ECO:0000305|PubMed:17401110, ECO:0000305|PubMed:18702514, ECO:0000305|PubMed:21652702, ECO:0000305|PubMed:26494624}; CATALYTIC ACTIVITY: Reaction=1,2,3-trioctanoylglycerol + H2O = dioctanoylglycerol + H(+) + octanoate; Xref=Rhea:RHEA:47864, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:25646, ChEBI:CHEBI:76978, ChEBI:CHEBI:88066; Evidence={ECO:0000269|PubMed:15287741, ECO:0000269|PubMed:17401110, ECO:0000269|PubMed:18702514, ECO:0000269|PubMed:21652702, ECO:0000269|PubMed:26494624};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47865; Evidence={ECO:0000305|PubMed:15287741, ECO:0000305|PubMed:17401110, ECO:0000305|PubMed:18702514, ECO:0000305|PubMed:21652702, ECO:0000305|PubMed:26494624}; CATALYTIC ACTIVITY: Reaction=1,2-didecanoylglycerol + H2O = decanoate + decanoylglycerol + H(+); Xref=Rhea:RHEA:48596, ChEBI:CHEBI:11152, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:27689, ChEBI:CHEBI:90605; Evidence={ECO:0000269|PubMed:15287741};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48597; Evidence={ECO:0000305|PubMed:15287741}; CATALYTIC ACTIVITY: Reaction=H2O + long chain 1,2-diacyl-3-O-beta-D-galactosyl-sn-glycerol = a fatty acid + H(+) + long chain acyl-3-O-beta-D-galactosyl-sn-glycerol; Xref=Rhea:RHEA:48700, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:28868, ChEBI:CHEBI:90477, ChEBI:CHEBI:90770; Evidence={ECO:0000305|PubMed:18702514};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48701; Evidence={ECO:0000305|PubMed:18702514}; CATALYTIC ACTIVITY: Reaction=1,2-dioctanoyl-3-O-beta-D-galactosyl-sn-glycerol + H2O = H(+) + octanoate + octanoyl-3-(beta-D-galactosyl)-sn-glycerol; Xref=Rhea:RHEA:48696, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:25646, ChEBI:CHEBI:90453, ChEBI:CHEBI:90769; Evidence={ECO:0000269|PubMed:20083229};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48697; Evidence={ECO:0000305|PubMed:20083229}; CATALYTIC ACTIVITY: Reaction=1,2-didodecanoyl-3-beta-D-galactosyl-sn-glycerol + H2O = dodecanoate + dodecanoyl-3-beta-D-galactosyl-sn-glycerol + H(+); Xref=Rhea:RHEA:48540, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:18262, ChEBI:CHEBI:90340, ChEBI:CHEBI:90515; Evidence={ECO:0000269|PubMed:15287741, ECO:0000269|PubMed:17401110, ECO:0000269|PubMed:18702514};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48541; Evidence={ECO:0000305|PubMed:15287741, ECO:0000305|PubMed:17401110, ECO:0000305|PubMed:18702514}; CATALYTIC ACTIVITY: Reaction=1-beta-D-galactosyl-2,3-didodecanoyl-sn-glycerol + H2O = 1-beta-D-galactosyl-dodecanoyl-sn-glycerol + dodecanoate + H(+); Xref=Rhea:RHEA:48536, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:18262, ChEBI:CHEBI:90342, ChEBI:CHEBI:90514; Evidence={ECO:0000269|PubMed:17401110};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48537; Evidence={ECO:0000305|PubMed:17401110}; CATALYTIC ACTIVITY: Reaction=1,2-diacyl-3-O-[alpha-D-galactosyl-(1->6)-beta-D-galactosyl]-sn-glycerol + H2O = a fatty acid + acyl-3-O-[alpha-D-galactosyl-(1->6)-beta-D-galactosyl]-sn-glycerol + H(+); Xref=Rhea:RHEA:48372, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:28396, ChEBI:CHEBI:28868, ChEBI:CHEBI:90310; Evidence={ECO:0000269|PubMed:26494624};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48373; Evidence={ECO:0000305|PubMed:26494624}; CATALYTIC ACTIVITY: Reaction=H2O + long chain 1,2-diacyl-3-O-[alpha-D-galactosyl-(1->6)-beta-D-galactosyl]-sn-glycerol = a fatty acid + H(+) + long chain acyl-3-O-[alpha-D-galactosyl-(1->6)-beta-D-galactosyl]-sn-glycerol; Xref=Rhea:RHEA:48708, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:28868, ChEBI:CHEBI:90463, ChEBI:CHEBI:90774; Evidence={ECO:0000269|PubMed:20083229};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48709; Evidence={ECO:0000305|PubMed:20083229}; CATALYTIC ACTIVITY: Reaction=1,2-dioctanoyl-3-O-[alpha-D-galactosyl-(1->6)-beta-D-galactosyl]-sn-glycerol + H2O = H(+) + octanoate + octanoyl-3-O-[alpha-D-galactosyl-(1->6)-beta-D-galactosyl]-sn-glycerol; Xref=Rhea:RHEA:48692, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:25646, ChEBI:CHEBI:90457, ChEBI:CHEBI:90768; Evidence={ECO:0000269|PubMed:20083229};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48693; Evidence={ECO:0000305|PubMed:20083229}; CATALYTIC ACTIVITY: Reaction=1,2-didodecanoyl-3-O-[alpha-D-galactosyl-(1->6)-beta-D-galactosyl]-sn-glycerol + H2O = dodecanoate + dodecanoyl-3-O-[alpha-D-galactosyl-(1->6)-beta-D-galactosyl]-sn-glycerol + H(+); Xref=Rhea:RHEA:48516, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:18262, ChEBI:CHEBI:90337, ChEBI:CHEBI:90359; Evidence={ECO:0000269|PubMed:17401110, ECO:0000269|PubMed:18702514};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48517; Evidence={ECO:0000305|PubMed:17401110, ECO:0000305|PubMed:18702514}; CATALYTIC ACTIVITY: Reaction=a 1,2-diacyl-sn-glycero-3-phosphocholine + H2O = a fatty acid + a monoacyl-sn-glycero-3-phosphocholine + H(+); Xref=Rhea:RHEA:44664, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:28868, ChEBI:CHEBI:57643, ChEBI:CHEBI:84465; Evidence={ECO:0000269|PubMed:17401110, ECO:0000269|PubMed:18702514};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44665; Evidence={ECO:0000305|PubMed:17401110, ECO:0000305|PubMed:18702514}; |
| DNA Binding | |
| EC Number | 3.1.1.26; 3.1.1.3 |
| Enzyme Function | FUNCTION: Lipase that primarily hydrolyzes triglycerides and galactosylglycerides (PubMed:15287741, PubMed:17401110, PubMed:19451396, PubMed:21865348, PubMed:20083229, PubMed:26494624, PubMed:18702514). In neonates, may play a major role in pancreatic digestion of dietary fats such as milk fat globules enriched in long-chain triglycerides (PubMed:23732775, PubMed:19824014, PubMed:21652702). Hydrolyzes short-, medium- and long-chain fatty acyls in triglycerides without apparent positional specificity (PubMed:15287741, PubMed:17401110, PubMed:21865348, PubMed:21652702, PubMed:18702514). Can completely deacylate triacylglycerols (PubMed:21865348). When the liver matures and bile salt synthesis increases, likely functions mainly as a galactolipase and monoacylglycerol lipase. Hydrolyzes monogalactosyldiglycerols (MGDG) and digalactosyldiacylglycerols (DGDG) present in a plant-based diet, releasing long-chain polyunsaturated fatty acids (PubMed:15287741, PubMed:17401110, PubMed:20083229, PubMed:26494624, PubMed:18702514). Hydrolyzes medium- and long-chain fatty acyls in galactolipids (PubMed:20083229, PubMed:18702514). May act together with LIPF to hydrolyze partially digested triglycerides (PubMed:23732775). Hydrolyzes long-chain monoglycerides with high efficiency (PubMed:17401110, PubMed:21652702, PubMed:23732775). In cytotoxic T cells, contributes to perforin-dependent cell lysis, but is unlikely to mediate direct cytotoxicity (By similarity). Also has low phospholipase activity (PubMed:17401110, PubMed:18702514). In neurons, required for the localization of the phospholipid 1-oleoyl-2-palmitoyl-PC (OPPC) to neurite tips through acyl chain remodeling of membrane phospholipids (By similarity). The resulting OPPC-rich lipid membrane domain recruits the t-SNARE protein STX4 by selectively interacting with the STX4 transmembrane domain and this promotes surface expression of the dopamine transporter SLC6A3/DAT at neurite tips by facilitating fusion of SLC6A3-containing transport vesicles with the plasma membrane (By similarity). {ECO:0000250|UniProtKB:P17892, ECO:0000250|UniProtKB:P54318, ECO:0000269|PubMed:15287741, ECO:0000269|PubMed:17401110, ECO:0000269|PubMed:18702514, ECO:0000269|PubMed:19451396, ECO:0000269|PubMed:19824014, ECO:0000269|PubMed:20083229, ECO:0000269|PubMed:21652702, ECO:0000269|PubMed:21865348, ECO:0000269|PubMed:23732775, ECO:0000269|PubMed:26494624}. |
| Temperature Dependency | |
| PH Dependency | BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is 8.8 for triacylglycerol lipase activity, 8.5 for phospholipase activity and 8 for galactolipase activity. The enzyme activities decrease in the pH 5-7 range corresponding to the physiological conditions occurring in the small intestine. {ECO:0000269|PubMed:17401110}; |
| Pathway | PATHWAY: Glycerolipid metabolism; triacylglycerol degradation. {ECO:0000269|PubMed:21865348}.; PATHWAY: Glycolipid metabolism. {ECO:0000269|PubMed:20083229}. |
| nucleotide Binding | |
| Features | Active site (3); Beta strand (27); Chain (1); Disulfide bond (6); Domain (1); Glycosylation (2); Helix (13); Metal binding (4); Mutagenesis (1); Natural variant (2); Region (2); Sequence conflict (2); Signal peptide (1); Turn (9) |
| Keywords | 3D-structure;Calcium;Cell projection;Cytoplasmic vesicle;Disulfide bond;Glycoprotein;Hydrolase;Lipid degradation;Lipid metabolism;Membrane;Metal-binding;Reference proteome;Secreted;Signal |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:18702514, ECO:0000269|PubMed:19824014}. Zymogen granule membrane {ECO:0000250|UniProtKB:P54318}; Peripheral membrane protein {ECO:0000250|UniProtKB:P54318}. Cell projection, neuron projection {ECO:0000250|UniProtKB:P54318}. Note=Localizes to neurite tips in neuronal cells. {ECO:0000250|UniProtKB:P54318}. |
| Modified Residue | |
| Post Translational Modification | |
| Signal Peptide | SIGNAL 1..17; /evidence=ECO:0000255 |
| Structure 3D | X-ray crystallography (2) |
| Cross Reference PDB | 2OXE; 2PVS; |
| Mapped Pubmed ID | 16385451; 16887271; 19548271; 21554982; 27662254; |
| Motif | |
| Gene Encoded By | |
| Mass | 51,961 |
| Kinetics | |
| Metal Binding | METAL 206; /note="Calcium; via carbonyl oxygen"; /evidence="ECO:0000269|PubMed:18702514, ECO:0007744|PDB:2OXE, ECO:0007744|PDB:2PVS"; METAL 209; /note="Calcium; via carbonyl oxygen"; /evidence="ECO:0000269|PubMed:18702514, ECO:0007744|PDB:2OXE, ECO:0007744|PDB:2PVS"; METAL 211; /note="Calcium"; /evidence="ECO:0000269|PubMed:18702514, ECO:0007744|PDB:2OXE, ECO:0007744|PDB:2PVS"; METAL 214; /note="Calcium"; /evidence="ECO:0000269|PubMed:18702514, ECO:0007744|PDB:2OXE, ECO:0007744|PDB:2PVS" |
| Rhea ID | RHEA:12044; RHEA:12045; RHEA:13189; RHEA:13190; RHEA:38575; RHEA:38576; RHEA:47868; RHEA:47869; RHEA:39955; RHEA:39956; RHEA:38487; RHEA:38488; RHEA:48024; RHEA:48025; RHEA:40475; RHEA:40476; RHEA:47864; RHEA:47865; RHEA:48596; RHEA:48597; RHEA:48700; RHEA:48701; RHEA:48696; RHEA:48697; RHEA:48540; RHEA:48541; RHEA:48536; RHEA:48537; RHEA:48372; RHEA:48373; RHEA:48708; RHEA:48709; RHEA:48692; RHEA:48693; RHEA:48516; RHEA:48517; RHEA:44664; RHEA:44665 |
| Cross Reference Brenda | 3.1.1.26; |